Hypoactivation and Dysconnectivity of a Frontostriatal Circuit During Goal-Directed Planning as an Endophenotype for Obsessive-Compulsive Disorder
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Peer-reviewed
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Background: The symptoms of Obsessive-Compulsive Disorder (OCD) have been postulated to result from impaired executive functioning and excessive habit formation at the expense of goal-directed control and have been objectively demonstrated using neuropsychological tests in such patients. This study tests whether there is functional hypoactivation as well as dysconnectivity of discrete frontostriatal pathways during goal-directed planning in OCD patients and in their unaffected first-degree relatives. Methods: Twenty-one comorbidity free OCD patients, 19 clinically asymptomatic first-degree relatives of these patients, and 20 control participants were tested on a functional magnetic resonance optimized version of the Tower of London task. Group differences in brain activation during goal-directed planning were measured together with associated frontostriatal functional connectivity. Results: OCD patients and their clinically asymptomatic relatives manifested hypoactivation of the right dorsolateral prefrontal cortex during goal-directed planning, coupled with reduced functional connectivity between this cortical region and the basal ganglia (putamen). Conclusions: Hypoactivation of cortical regions associated with goal-directed planning, and associated frontostriatal dysconnectivity, represent a candidate endophenotype for OCD. These findings accord with abnormalities in neural networks supporting the balance between goal-directed and habitual behavior, with implications for recent neuropsychological theories of OCD and the major neurobiological model for this disorder.
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2451-9030
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Wellcome Trust (110049/Z/15/Z)
Medical Research Council (G0001354)
Medical Research Council (G1000183)